Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
Am J Physiol Renal Physiol. 2010 Oct;299(4):F752-7. doi: 10.1152/ajprenal.00324.2010. Epub 2010 Jul 28.
The physiology of glomerular permselectivity remains mechanistically obscure, despite its importance in human disease. Although electrical contributions to glomerular permselectivity have long been considered important, two recent reports demonstrated enhanced glomerular permeability to anionic versus neutral polysaccharides. The interpretation of these observations is complicated by confounding of the effects of chemical modification on charge with effects on size and shape. In this report, neutral and anionic Ficoll are characterized by size-exclusion chromatography with online light scattering and viscometry and filtration through a highly defined anionic filtration membrane. Neutral and carboxymethylated Ficoll are nearly identical in size and conformation, yet carboxymethylated Ficoll is retained by an anionic membrane in excess of neutral Ficoll. This suggests that comparisons between clearances of neutral and carboxymethylated Ficoll may be a sensitive probe of electrostatic interactions independent of size and conformation.
尽管肾小球滤过选择性在人类疾病中具有重要意义,但其机制仍不清楚。尽管电作用对肾小球滤过选择性的重要性早已被人们所认识,但最近有两项研究表明,带负电荷的多糖相对于中性多糖具有更高的肾小球通透性。这两项观察结果的解释因电荷对大小和形状的影响与化学修饰的效果相混淆而变得复杂。在本报告中,通过尺寸排阻色谱法与在线光散射和粘度测定以及通过高度定义的阴离子过滤膜进行过滤,对中性和阴离子 Ficoll 进行了表征。中性和羧甲基化 Ficoll 在大小和构象上几乎相同,但羧甲基化 Ficoll 比中性 Ficoll 更能被阴离子膜保留。这表明,中性和羧甲基化 Ficoll 清除率之间的比较可能是一种敏感的探测静电相互作用的方法,而不依赖于大小和构象。